Binding polypeptides, such as antibodies and fragments thereof, are commercially important as therapeutic and diagnostic agents. Traditional methods of screening for binding polypeptide generally employ soluble antigens. However, for certain cell-surface antigens, conformational epitopes on these antigens are altered when the antigens are solubilized from the plasma membrane, resulting in a failure to generate binding polypeptides that can recognize the native antigen. Accordingly, there is a need in the art for novel methods of screening for binding polypeptides that can specifically bind to cell-surface antigens in their native conformation.